Reactome | Integrin alphaIIb beta3 activation

Integrin alphaIIb beta3 activation

Stable Identifier

R-HSA-354077

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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The interaction between talin and integrin alphaIIb beta3 breaks the putative salt bridge between the alphaIIb (R995) and beta3 (D723) integrin chains and induces conformational changes in their external domains increasing their affinity for fibrinogen and other ECM ligands. Breaking of this salt bridge is necessary but not sufficient for full activation.
The Talin F3 subdomain of the FERM domain has a phosphotyrosine binding (PTB) domain fold. This domain interacts with the membrane-proximal (MP) region within the integrin beta3 chain. The primary function of this interaction is to provide an initial strong linkage between talin and integrin and this interaction holds the key to the molecular recognition required for activation. In platelets SRC kinase and its negative regulator CSK associates constitutively with integrin alphaIIbbeta3. SRC is involved in alphaIIbbeta3 dependent activation of SYK, and both SRC and SYK are required to initiate cytoskeletal events responsible for platelet spreading on fibrinogen.

Literature References

PubMed ID	Title	Journal	Year
10446041	Integrin signaling Giancotti, FG, Ruoslahti, E	Science	1999
14754902	Integrin activation Calderwood, DA	J Cell Sci	2004
17218263	Structural basis of integrin activation by talin Wegener, KL, Partridge, AW, Han, J, Pickford, AR, Liddington, RC, Ginsberg, MH, Campbell, ID	Cell	2007
11940607	Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton Obergfell, A, Eto, K, Mocsai, A, Buensuceso, C, Moores, SL, Brugge, JS, Lowell, CA, Shattil, SJ	J Cell Biol	2002
18434644	Talin at a glance Critchley, DR, Gingras, AR	J Cell Sci	2008